Potentially inappropriate medication on communitydwelling older adults: Longitudinal analysis using the International Mobility in Aging Study. / Medicación potencialmente inapropiada en adultos mayores de la comunidad: análisis longitudinal del estudio IMIAS

Introduction: Medications are a fundamental part of the treatment of multiple pathologies. However, despite their benefits, some are considered potentially inappropriate medications for older people given their safety profile. Epidemiological data differences related to potentially inappropriate medications make it difficult to determine their effects on elderly people. Objective: To estimate the prevalence and types of potentially inappropriate medications using the 2019 Beers Criteria® in a cohort of adults older than 65 years. Materials and methods: We performed an observational, multicenter, retrospective, longitudinal study of a four-year follow-up of potentially inappropriate medications in community-dwelling older adults. Results: We followed 820 participants from five cities for four years (2012-2016) and evaluated them in three different moments (m1 = 2012, m2 = 2014, and m3 = 2016). The average age was 69.07 years, and 50.9% were women. The potentially inappropriate medication prevalence in the participants was 40.24%. The potentially inappropriate medications' mean among the studied subjects in the first moment was 1.65 (SD = 0.963), in the second was 1.73 (SD = 1.032), and in the third was 1.62 (SD = 0.915). There were no statistical differences between measurements (Friedman test, value = 0.204). The most frequent potentially inappropriate medications categories were gastrointestinal (39.4%), analgesics (18.8%), delirium-related drugs (15.4%), benzodiazepines (15.2%), and cardiovascular (14.2%). Conclusions: About half of the population of the community-dwelling older adults had prescriptions of potentially inappropriate medications in a sustained manner and without significant variability over time. Mainly potentially inappropriate medications were gastrointestinal and cardiovascular drugs, analgesics, delirium-related drugs, and benzodiazepines.

Introducción. Los fármacos son parte fundamental del tratamiento de múltiples enfermedades. Sin embargo, a pesar de sus beneficios, algunos se consideran medicamentos potencialmente inapropiados en adultos mayores, dado su perfil de seguridad. Las diferencias en los datos epidemiológicos relacionados con los medicamentos potencialmente inapropiados dificultan el establecimiento de sus efectos en adultos mayores. Objetivo. Estimar la prevalencia longitudinal y los tipos de medicamentos potencialmente inapropiados, utilizando los criterios Beers® del 2019 en una cohorte de adultos mayores de 65 años. Materiales y métodos. Se realizó un estudio observacional, multicéntrico, retrospectivo y longitudinal, de cuatro años de seguimiento de los medicamentos potencialmente inapropiados en adultos mayores de la comunidad. Resultados. Se evaluaron 820 participantes de cinco ciudades durante cuatro años (2012 a 2016) en tres momentos (m1: 2012, m2: 2014 y m3; 2016). La edad promedio fue de 69,07 años y el 50,9 % eran mujeres. La prevalencia de medicamentos potencialmente inapropiados en los participantes fue del 40,24 %. El promedio de estos medicamentos entre los sujetos estudiados en el primer momento fue de 1,65 (DE = 0,963), en el segundo fue de 1,73 (DE = 1,032) y en el tercero fue de 1,62 (DE = 0,915). No hubo diferencias estadísticas entre las mediciones (prueba de Friedman, p = 0,204). Las categorías de los medicamentos potencialmente inapropiados más frecuentes fueron: gastrointestinales (39,4 %), analgésicos (18,8 %), relacionados con delirium (15,4 %), benzodiacepinas (15,2 %) y cardiovasculares (14,2 %). Conclusiones. En cerca de la mitad de la población de adultos mayores de la comunidad, se prescribieron medicamentos potencialmente inapropiados de manera sostenida y sin variabilidad importante en el tiempo. Los más recetados fueron aquellos para tratar malestares gastrointestinales y cardiovasculares, analgésicos, para el delirium y benzodiacepinas.

[Comparison of the efficacy of remimazolam and propofol on hemodynamics and quality of early postoperative recovery in elderly patients with frailty undergoing endoscopic retrograde cholangiopancreatography].

Objective: To compare the efficacy of remimazolam and propofol on hemodynamics and quality of early postoperative recovery in elderly patients with frailty undergoing endoscopic retrograde cholangiopancreatography (ERCP). Methods: A total of 108 elderly patients with frailty (aged≥75 years) undergoing elective ERCP in the General Hospital of Northern Theater Command were prospectively enrolled from November 2022 to May 2023. According to the different anesthetic drugs used, the patients were divided into two groups by random number table method: remimazolam group (group R) and propofol group (group P). The group R was given remimazolam 0.15-0.20 mg/kg and alfentanil 5.0 µg/kg for anesthesia onset, and then was pumped remimazolam 0.4-0.8 mg·kg-1·h-1 and alfentanil 0.5 µg·kg-1·min-1 to maintain sedation. The group P was given propofol 1.0-1.5 mg/kg and alfentanil 5.0 µg/kg, and was pumped propofol 2.0-6.0 mg·kg-1·h-1 and alfentanil 0.5 µg·kg-1·min-1. The primary outcome was the incidence of intraoperative hypotension [mean arterial pressure (MAP)<65 mmHg (1 mmHg=0.133 kPa) or MAP>20% decrease from baseline value] and severe hypotension (MAP<55 mmHg) in both groups, and other outcomes included: MAP, heart rate, pulse oxygen saturation (SpO2) and bispectral index (BIS) values of patients at each time of before anesthesia induction (T0), 1 min after anesthesia induction (T1), endoscope through the oropharynx (T2), immediate lithotomy (T3), endoscope withdrawal from the oropharynx (T4), and patients awake (T5); the use of vasoactive drug during operation; the incidence of bradycardia, hypoxemia and injection pain; and the postoperative 15-item Quality of Recovery (QoR-15) score. Results: Group R included 33 males and 20 females, aged (81.5±4.9) years. Group P included 26 males and 29 females, aged (82.3±6.0) years. The incidence of intraoperative hypotension in group R was 24.5% (13/53), which was lower than 43.6% (24/55) in group P (P=0.036), there was no significant difference of the incidence of severe hypotension which was 0 (0/53) and 5.5% (3/55) (P=0.225). Compared with T0, MAP and BIS decreased at T1-T4 (both P<0.05); heart rate and SpO2 decreased at T1-T2 in both groups (both P<0.05). Compared with group P, MAP increased at T1-T4; heart rate, SpO2 and BIS increased in group R (all P<0.05). The use of intraoperative vasoactive drug in group R was (93.9±21.4) µg, lower than (123.3±29.7) µg in group P (P<0.001), and the incidence of bradycardia, hypoxemia and injection pain in group R was 5.7% (3/53), 13.2% (7/53), and 3.8% (2/53), lower than 18.2% (10/55), 30.9% (17/55), and 16.4% (9/55) in group P (all P<0.05). There was no significant difference in the incidence of bucking or involuntary body movement and hiccuping in both groups (both P>0.05). The awakening time in group R was (11.8±3.0) min, longer than (10.3±3.3) min in group P (P=0.016), and the incidence of emergence agitation was 3.8% (2/53), lower than 16.4% (9/55) (P=0.031). There was no significant difference in postanesthesia care unit (PACU) stay duration and the incidence of postoperative nausea and vomiting in both groups (all P>0.05). The postoperative QoR-15 scores at 1 d were (131.9±4.7) and (129.3±5.7) with statistically significant difference (P=0.010), and QoR-15 scores at 3 d were (134.8±3.3) and (133.6±5.0) with no significant difference (P=0.205). Conclusions: Compared with propofol, remimazolam reduces the incidence of intraoperative hypotension, bradycardia, injection pain and the use of intraoperative vasoactive drug on elderly patients with frailty undergoing ERCP. Remimazolam has relatively stable hemodynamics, it prolongs the recovery time but does not significantly affect the quality of early postoperative recovery.

The Effect of Lidocaine-Prilocaine Cream Combined with or Without Remimazolam on VAS and APAIS Anxiety Score in Patient Undergoing Spinal Anesthesia.

Purpose: This study aimed to investigate patients' expectative pain of spinal anesthesia puncture and anxiety pre-anesthesia, and to examine the effect of lidocaine-prilocaine cream and remimazolam prior to spinal anesthesia puncture on pain relief and anxiety release. Methods: Patients undergoing spinal anesthesia were divided into control, lidocaine-prilocaine cream, and lidocaine-prilocaine cream with remimazolam groups. A questionnaire consisting of The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and patient's concerns and Visual Analog Scale (VAS) was used to evaluate patient's anxiety and pain. The primary outcomes were differences in VAS and anxiety scores. Patient's spinal anesthesia-related concerns, advent events and hemodynamic index were also recorded. Results: The expected spinal anesthesia puncture pain was 5.34±0.27 and anxiety scores before spinal anesthesia was 10.88 ± 0.64. A statistically significant positive correlation of 31.3% was detected between VAS and APAIS scores (r = 0.313; P=0.003). The VAS score at the time of puncture decreased by 29.7% (3.78±0.40, P=0.001) in lidocaine-prilocaine cream group and 29.2% (3.75±0.39, P=0.001) in lidocaine-prilocaine cream with remimazolam group compared with the expected VAS score. Lidocaine-prilocaine cream combined with or without remimazolam reduced the percentage of moderate pain (21.4% and 31.3% vs 50.0%, P=0.0001) and increased mild pain (60.7% vs 59.4% vs 22.7%, P=0.03). Anxiety score in lidocaine-prilocaine cream group was reduced by 2.84 (8.04±0.76 vs 10.88 ± 0.46, P=0.05) when compared with pre-anesthesia. Concerns about postoperative pain (P=0.03) and fear of the needle or intervention (P=0.000) both decreased post-anesthesia among groups. Conclusion: Approximately half of the patients scheduled for spinal anesthesia experienced a moderate level of preoperative anxiety. The patient's pain expectation from the spinal anesthesia puncture was moderate, which was higher than the actual pain. Lidocaine-prilocaine cream with or without remimazolam sedative before spinal anesthesia puncture reduced the patient's pain and anxiety scores after surgery.

Remimazolam in General Anesthesia: A Comprehensive Review of Its Applications and Clinical Efficacy.

Remimazolam is a novel ultra-short-acting benzodiazepine with a unique pharmacokinetic profile that makes it an attractive option for use in general anesthesia. This review paper provides an in-depth analysis of remimazolam's applications in the field of general anesthesia, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential advantages compared to other anesthetic agents. Remimazolam acts on GABAa receptors, offering rapid onset and recovery times due to its unique metabolic pathway involving tissue esterases. Clinical trials have demonstrated its efficacy in procedural sedation and general anesthesia, showing a favorable safety profile with minimal cardiovascular and respiratory depression. Compared to traditional anesthetics such as propofol, remimazolam presents distinct advantages, including predictable pharmacokinetics, reduced risk of prolonged sedation, and a reliable safety margin. These attributes position remimazolam as a promising agent in various clinical settings. The purpose of this review is to synthesize current evidence on remimazolam and discuss its potential to improve clinical outcomes in anesthesia practice.

Olanzapine during lactation: impact on testicular morphometry and endocrine parameters in adult wistar rats.

Olanzapine (OLZ) is an antipsychotic medication used to treat postpartum psychiatric symptoms. It aimed to evaluate the effects of administering OLZ to lactating rats on testicular parameters of adult Wistar rats. Mothers received 2.5, 5 or 10 mg/kg until weaning. Adult male rats showed decrease in body weight, weight of testes, epididymis, prostate, seminal gland and gonadosomatic index when higher doses of OLZ were administered. Testicular volumetric parameters, as well as the length of seminiferous tubules, were also reduced in animals treated with the highest doses of OLZ. The diameter of the seminiferous tubules and the height of the seminiferous epithelium were reduced. There was also a relevant decrease in the population of Sertoli cells and a relevant reduction in the volume of individual Leydig cells. Histopathological analysis of the testes showed lesions compatible with testicular degeneration in rats treated with the highest dose of OLZ. There was a significant reduction in plasma testosterone levels in all treatments. It is noted, therefore, that the adverse impact on the testes of the highest doses of the drug during the neonatal period persisted into adulthood, with the dose of 2.5 mg/kg of OLZ proving to be safer than the others.

Effects of Propofol, Low and High Doses of Remimazolam on Hemodynamic and Inflammatory Response in Laparoscopic Surgery.

Background: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery. Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II-III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups. Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels. Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.

Opioid and benzodiazepine requirements in critically ill post-surgical children with down syndrome: a systematic review and meta-analysis.

BACKGROUND: Down syndrome (DS), or Trisomy 21, is defined by the existence of an additional chromosome 21. Various physiological considerations in DS patients might lead to challenges in adequate pain management and sedation after surgery. The aim of this systematic review and meta-analysis is to evaluate the variations of the requirement needed for pain management and sedation in patients with DS who have undergone surgery compared to patients without DS. METHODS: A systematic review and meta-analysis of studies were conducted, focusing on critically ill patients with DS who were admitted to Intensive care units (ICUs) post-surgery and received opioids and/or benzodiazepines. Searches were conducted in four databases from their inception to November 18, 2023 (Pubmed, Scopus, Cochrane Library, and Web of Science). The primary outcome measured was the dosage of Oral Morphine Equivalent (OME) administered in the days following surgery. Fixed-effect models were used, an approach advisable when only a limited number of studies are available. RESULTS: Out of the 992 studies initially screened, the systematic review included ten studies, encompassing 730 patients, while the meta-analysis consisted of seven studies, encompassing 533 patients. Of the seven studies included in the analysis, 298 patients were identified to have DS, and 235 patients served as controls. Patients with DS showed a slight increase in OME needs on the first day, but this increase was not statistically significant (mean difference [MD] = 0.09; 95% Confidence Interval [CI]: [-0.02, 0.20]; P = 0.11). There was also no significant difference in the requirement for Midazolam on the first day among DS patients (MD = 0.01; CI [-0.16, 0.19]; P = 0.88). In addition, the duration of mechanical ventilation was not statistically significant in patients with DS compared with the control group (MD = -1.46 hours; 95% CI [-9.74, 6.82]; P = 0.73). CONCLUSION: Patients with Down syndrome did not require more sedation or analgesia in the first three days after surgery than patients without Down syndrome. Additionally, the two groups showed no significant difference in the duration of mechanical ventilation.

Software-assisted automated detection and identification of "unknown" analogues of benzodiazepines in liquid chromatography mass spectrometry analysis.

RATIONALE: Benzodiazepines (BZDs) construct a large group of psychoactive drugs acting as depressants of the central nervous system (CNS) and used in medicine as sedatives and anxiolytic and antiepileptic agents. The illicit use of these materials is a worldwide problem, and for many years, part of the benzodiazepines have been abused as rape drugs. For example, flunitrazepam (Rohypnol) is most commonly linked by media reports to drug-facilitated sexual assaults, more commonly referred to as "date rape." Furthermore, there are growing concerns for other misuses of these drugs. Over the last few years, there was an increase in the number, type, and availability of new psychoactive substances (NPS) belonging to the benzodiazepine group, challenging standard forensic labs to fully identify the chemical structure of new, unknown benzodiazepines. METHODS: This work demonstrates a new application of the automated tool for the detection and identification of benzodiazepine analogues using high-resolution-accurate-mass LC-MS analysis, followed by "Compound Discoverer" (CD) software data processing, to automatically detect various benzodiazepine analogues by picking peaks and compare them to in silico calculated modifications made on a predefined basic backbone. Subsequently, a complete structural elucidation for the proposed molecular formula is obtained by MS/MS data analysis of the suspected component. RESULTS: This method was found to be useful for the automated detection and putative identification of a series of nine "unknown" benzodiazepine analogues, at concentrations in the low ng/mL range. CONCLUSIONS: We hereby present a general demonstration of this powerful tool for the forensic community in the detection and identification of hazardous unknown compounds.

Remimazolam As a Sole Sedative Agent for Gastrostomy Tubes Placed in the Interventional Radiology Suite: A Case Series.

Remimazolam is an ultrashort acting intravenous sedative-hypnotic approved for procedural sedation. We report a series of 8 cases of radiographically placed gastrostomy tubes using remimazolam as the sole anesthetic agent. Interventional radiology (IR) gastrostomy tube placement entails anesthetizing often complex patients in a nonoperating room environment. All 8 patients reported here underwent successful gastrostomy tube placement without the need for conversion to general anesthesia. Remimazolam is a feasible option to sedate patients for gastrostomy tube placement in the IR suite.

Comparative study on the impact of remimazolam and sevoflurane on quality of recovery after transurethral resection of bladder tumor: A randomized controlled noninferiority study.

BACKGROUND: Remimazolam is manifested by rapid action, hemodynamic stability, and fast recovery. Our study aimed to investigate whether the quality of recovery (QoR) after remimazolam anesthesia in patients undergoing transurethral resection of bladder tumor, which is predominantly performed in the elderly population, is not inferior to that after conventional anesthesia using sevoflurane. METHODS: Thirty-four patients were randomly allocated into either of group S (n = 17, receiving sevoflurane anesthesia), or group R (n = 17, receiving remimazolam anesthesia). The QoR was assessed by Korean version of QoR-15 questionnaire, on the day before and after the surgery. Scores acquired for each individual item, QoR-15 scores categorized into 5 dimensions (physical comfort, physical independence, psychological support, emotional state, and pain), and overall global score were subjected to comparative analysis. The primary outcome was postoperative global QoR-15, and a noninferiority delta value of 8.0 was employed. RESULTS: The postoperative global QoR-15 in the group S was 141 (134-146), and in the groups R was 133 (128-142) (P = .152). The mean difference of global QoR-15 (group S-group R) was 1.471 (95% confidence interval of -10.204 to 13.146), and the lower 95% confidence interval margin was lower than the noninferiority margin of -8.0. When comparing the QoR-15 sorted by 5 dimensions, pain scored higher in the group S (20 [18-20]) compared to the group R (15 [15-20], P = .032). CONCLUSION: The postoperative QoR following transurethral resection of bladder tumor was found to be lower in patients anesthetized with remimazolam in comparison to those anesthetized with sevoflurane.

Deprescribing benzodiazepine receptor agonists in older adults: a mixed-methods study to adapt the Canadian D-PRESCRIBE intervention to the Belgian community setting.

OBJECTIVE: Guidelines recommend deprescribing benzodiazepine receptor agonists (BZRA) in older adults, yet implementation in clinical practice remains limited. Adapting effective, evidence-based interventions to a new context is a resource-saving strategy. In Canada, the D-PRESCRIBE intervention comprised a patient educational brochure and a pharmaceutical opinion inviting physicians to revise BZRA prescribing and consider safer alternatives. Due to its effectiveness on BZRA deprescribing among Canadian older adults, we aimed to adapt the D-PRESCRIBE intervention to the Belgian community setting. DESIGN: Recommendations from the ADAPT guidance, that provides a systematic approach for adapting interventions to new contexts, were followed. We conducted a mixed-methods study that comprised (1) group discussions and cognitive interviews to assess the acceptability and need for adaptation of the intervention's components and (2) a survey on the adapted pharmaceutical opinion. A research committee involving stakeholders' representatives decided on the adaptations, respecting the core functions of both tools. Changes in intervention components were reported following the Model for Adaptation Design and Impact framework. SETTING: Belgian French-speaking community setting. PARTICIPANTS: Six older adults (≥65 years), six general practitioners (GPs) and seven pharmacists participated in the group discussions or interviews. 46 GPs and 91 pharmacists responded to the survey. RESULTS: Participants welcomed the brochure positively. Still, some changes in the vocabulary, wording, photos and icons were made for several purposes including making the patient feel concerned about the brochure and softening the use of fear. The pharmaceutical opinion aroused mixed perceptions. Its name, layout and content were adapted to enhance its acceptability and fit with our healthcare system, practices and national guidelines. The survey highlighted several enablers and barriers to its use from the perspectives of GP and pharmacist. CONCLUSIONS: The Canadian D-PRESCRIBE intervention was adapted to the Belgian setting following a thorough and transparent process. Its feasibility will be tested in a future pilot study (NCT:05929417).

The influence of sex on the dosage of remimazolam co-administered with remifentanil for loss of consciousness in adult patients: an up-and-down sequential allocation trial.

BACKGROUND: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences. METHODS: Using a modified Dixon's up-and-down allocation approach, we sequentially enrolled male and female patients aged 19-60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer's Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved. RESULTS: We included 22 male and 22 female patients. Based on Dixon's up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18-0.20) mg/kg in the male group and 0.29 (0.29-0.30) mg/kg in the female group. CONCLUSIONS: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients. TRIAL REGISTRATION: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022).

Evaluation of Clinical Correlation between Insulin Resistance and Antipsychotic Drug Therapy in Patients with Schizophrenia.

BACKGROUND: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone. METHOD: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment. RESULTS: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05). CONCLUSIONS: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.

Onset of Prolonged High-Potency Benzodiazepine Use Among ICU Survivors: A Nationwide Cohort Study.

OBJECTIVES: Exposure to critical illness and intensive care may lead to long-term psychologic and physical impairments. To what extent ICU survivors become prolonged users of benzodiazepines after exposure to critical care is not fully explored. This study aimed to describe the extent of onset of prolonged high-potency benzodiazepine use among ICU survivors not using these drugs before admission, identify factors associated with this use, and analyze whether such usage is associated with increased mortality. DESIGN: Retrospective cohort study. SETTING: Sweden, including all registered ICU admissions between 2010 and 2017. PATIENTS: ICU patients surviving for at least 3 months, not using high-potency benzodiazepine before admission, were eligible for inclusion. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: A total of 237,904 patients were screened and 137,647 were included. Of these 5338 (3.9%) became prolonged users of high-potency benzodiazepines after ICU discharge. A peak in high-potency benzodiazepine prescriptions was observed during the first 3 months, followed by sustained usage throughout the follow-up period of 18 months. Prolonged usage was associated with older age, female sex, and a history of both somatic and psychiatric comorbidities, including substance abuse. Additionally, a longer ICU stay, a high estimated mortality rate, and prior consumption of low-potency benzodiazepines were associated with prolonged use. The risk of death between 6 and 18 months post-ICU admission was significantly higher among high-potency benzodiazepine users, with an adjusted hazard ratio of 1.8 (95% CI, 1.7-2.0; p < 0.001). No differences were noted in causes of death between users and nonusers. Conclusions: Despite the lack of evidence supporting long-term treatment, prolonged usage of high-potency benzodiazepines 18 months following ICU care was notable and associated with an increased risk of death. Considering the substantial number of ICU admissions, prevention of benzodiazepine misuse may improve long-term outcomes following critical care.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan.

BACKGROUND: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. METHODS: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. FINDINGS: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. INTERPRETATION: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. FUNDING: National Science and Technology Council.

Catatonia.

Catatonia is a neuropsychiatric disorder characterized by motor, affective and cognitive-behavioural signs, which lasts from hours to days. Intensive research over the past two decades has led to catatonia being recognized as an independent diagnosis in the International Classification of Diseases, 11th Revision (ICD-11) since 2022. Catatonia is found in 5-18% of inpatients on psychiatric units and 3.3% of inpatients on medical units. However, in an unknown number of patients, catatonia remains unrecognized and these patients are at risk of life-threatening complications. Hence, recognizing the symptoms of catatonia early is crucial to initiate appropriate treatment to achieve a favourable outcome. Benzodiazepines such as lorazepam and diazepam, electroconvulsive therapy, and N-methyl-D-aspartate antagonists such as amantadine and memantine, are the cornerstones of catatonia therapy. In addition, dopamine-modulating second-generation antipsychotics (for example, clozapine and aripiprazole) are effective in some patient populations. Early and appropriate treatment combined with new screening assessments has the potential to reduce the high morbidity and mortality associated with catatonia in psychiatric and non-psychiatric settings.

[Comparison of the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery].

Objective: To compare the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery. Methods: Prospectively, 60 pediatric patients, American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ, scheduled to undergo binocular strabismus daytime surgery in Beijing Tongren Hospital under general anesthesia with laryngeal mask airway from December 2021 to May 2022 were selected. They were randomly divided into Remimazolam group and Propofol group with 30 cases in each group, according to the ratio of 1∶1 by SPSS program. Patients in Remimazolam group were induced by remimazolam, remifentanil and micuronium chloride, and maintained by remimazolam and remifentanil. Patients in Propofol group were induced by propofol, remifentanil and micuronium chloride, and maintained by propofol and remifentanil. Patients in Remimazolam group were given 0.1 mg of flumazenil for antagonism 3 minutes after operation, while children in Propofol group waited for natural awakening. The primary outcome was the time from drug withdrawal to laryngeal mask removal after operation. The secondary outcomes included the time for consciousness loss during induction, intraoperative hemodynamic data [mean arterial pressure (MAP) and heart rate], the success rate of sedation, the awareness rate during operation, and the incidence of adverse events after admission to postanesthesia care unit(PACU). Results: The Remimazolam group included 12 males and 18 females, aged (5.0±1.4) years. There were 14 males and 16 females in the Propofol group, aged (5.3±1.3) years. The time from drug withdrawal to laryngeal mask removal in Remimazolam group was (6.5±1.2) min, which was shorter than that in Propofol group of (10.7±1.9) min (P<0.001). The time for consciousness loss during induction was (38.1±4.8) s in Remimazolam group, which was longer than that in Propofol group of (31.6±4.9) s (P<0.001). The variability of MAP and heart rate of patients during operation in Remimazolam group was lower than that in Propofol group (all P<0.05). There was no significant difference in sedation success rate, intraoperative awareness and adverse reactions in PACU between the two groups (all P>0.05). Conclusion: In pediatric patients with binocular strabismus during daytime surgery, general anesthesia with remimazolam can shorten the time from drug withdrawal to laryngeal mask removal after operation without increasing the incidence of postoperative adverse reactions and can provide more stable hemodynamics.

Comparative efficacy and safety of olanzapine and risperidone in the treatment of psychiatric and behavioral symptoms of Alzheimer's disease: Systematic review and meta-analysis.

OBJECTIVES: Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers. DESIGN: Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively. DATA SOURCES: Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang. ELIGIBILITY CRITERIA: Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD. DATA EXTRACTION AND SYNTHESIS: Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis. RESULTS: A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; P = .0008), and 0.62 (95% CI: 0.50-0.78; P < .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone. CONCLUSION: Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer's disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs.